Grabowski Patricia, Maaser Kerstin, Hanski Christoph, Stein Harald, Sturm Isrid, Hopfenmüller Werner, Dörken Bernd, Buhr Heinz-Johannes, Zeitz Martin, Scherübl Hans
Medical Clinic I, Gastroenterology, Infectious Diseases, Rheumatology, Charité--Campus Benjamin Franklin, Berlin, Germany.
Onkologie. 2005 Aug;28(8-9):399-403. doi: 10.1159/000086514. Epub 2005 Aug 29.
Recently, we have analyzed new prognostic markers in colorectal cancer including neuroendocrine differentiation, overexpression of the sialyl-Lex antigen, overexpression of the peripheral benzodiazepine receptor (PBR), BAX protein expression and p53 mutational status. The predictive power of all markers in combination has not yet been evaluated.
Between 1989 and 1991, 48 consecutive patients underwent surgery for stage III colorectal cancer at our hospital. All patients received a complete 5-year follow-up. Paraffin-embedded tumor samples were analyzed for all 5 markers. Multivariate discriminant analysis was performed to determine the prognostic value of all markers in combination.
Based on these prognostic markers a mathematical discriminant function was obtained. This function allowed to correctly predict the further course of disease in 77% of the patients (specificity: 83.3%, sensitivity: 70.8%). The discriminant function was confirmed in another group of 19 patients. Single marker analysis allowed the prediction of the further course of disease only in 58-70%.
Our study shows that in colorectal cancer, multimarker analysis is superior to unimarker analysis in predicting prognosis. The derived discriminant function allows patient stratification according to risk. Therefore, a multimarker analysis provides a rationale for future individualized risk-adapted therapies in stage III colorectal cancer.
最近，我们分析了结直肠癌的新预后标志物，包括神经内分泌分化、唾液酸化路易斯抗原的过表达、外周苯二氮䓬受体（PBR）的过表达、BAX蛋白表达和p53突变状态。尚未评估所有标志物联合使用时的预测能力。
1989年至1991年间，我院48例连续的III期结直肠癌患者接受了手术。所有患者均接受了完整的5年随访。对石蜡包埋的肿瘤样本进行了所有5种标志物的分析。进行多变量判别分析以确定所有标志物联合使用时的预后价值。
基于这些预后标志物获得了一个数学判别函数。该函数能够正确预测77%患者的疾病进展（特异性：83.3%，敏感性：70.8%）。该判别函数在另一组19例患者中得到了验证。单标志物分析仅能预测58%-70%患者的疾病进展。
我们的研究表明，在结直肠癌中，多标志物分析在预测预后方面优于单标志物分析。所推导的判别函数可根据风险对患者进行分层。因此，多标志物分析为III期结直肠癌未来的个体化风险适应性治疗提供了理论依据。
